G-protein-coupled receptors (GPCRs) in the treatment of diabetes: Current view and future perspectives

Publication date: April 2018Source: Best Practice &Research Clinical Endocrinology &Metabolism, Volume 32, Issue 2Author(s): Guido Sebastiani, Elena Ceccarelli, Maria Grazia Castagna, Francesco DottaG-protein coupled receptors (GPCRs) represent the largest receptor family in the genome and are of great interest for the design of novel drugs in a wide variety of diseases including neurologic disorders, obesity and Type 2 diabetes mellitus. The latter is a chronic disease characterized by insulin resistance and impaired insulin secretion, affecting>400 million patients worldwide.Here we provide an overview on: a) The molecular basis of GPCR signalling and of its involvement in the regulation of insulin secretion and of glucose homeostasis; b) the role of GPCRs in type 2 diabetes pathophysiology and as therapeutic targets of current and future glucose-lowering drugs.

Conclusion: The TEMD Obesity Study shows that obesity is a major determinant of the poor metabolic control in patients with type 2 diabetes. These results underline the importance of prevention and management of obesity to improve health care in patients with type 2 diabetes. Also, the results point out the independent sociodemographic and clinical associates of obesity, which should be the prior targets to overcome, in the national fight with obesity.Obes Facts 2019;12:167 –178

Metabolic surgery is the most effective therapy for patients with type 2 diabetes mellitus (T2D) also improving diabetic kidney disease. Whether these effects depend on weight loss is currently unknown.

Abstract
Much of the cardiovascular disease burden and mortality can be traced back to four adverse health behaviors (smoking, poor diet, elevated body mass index, sedentary lifestyle) and three major risk factors (hypercholesterolemia, hypertension, diabetes). Ideal cardiovascular health defined as having all seven factors at goal is very rare among US adults. It is estimated that 87% of middle-aged US adults and 95% of individuals ≥60 years old meet ≤4 of these health metrics.1 Detailed guidelines are available that discuss cardiovascular risk assessment, lifestyle management, and treatment of individual r...

The objective of this study was to investigate mechanisms involved in palmitic acid-induced cardiomyocyte apoptosis. Human adult ventricular cardiomyocyte line (AC16 cells) exposed to high physiological levels of PA for 16 h showed enhanced transcription and phosphorylation of c-fos and c-jun subunits of AP-1 and transcription of caspase 8. When AC16 cells were transfected with small interfering RNA specific against p38α MAPK (si-p38α) for 24 or 48 h, the amplified phosphorylation of c-fos was dose-dependently attenuated, and procaspase 8 was dose-de pendently reduced. With translational knockdow...

Authors: Wang FG, Bai RX, Yan WM, Yan M, Dong LY, Song MM
Abstract
The modulation of the gut microbiota was recently deemed one of the mechanisms responsible for the excellent outcomes of bariatric surgery. However, to date, only few studies have assessed this, and they have high heterogeneity. In the present study, next-generation 16S ribosomal DNA amplicon sequencing was used to characterize the gut microbiota of healthy volunteers, as well as patients prior to and after sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB). Significant differences in α diversity, β diversity and species were iden...

Mihai
The Mediterranean diet originates in the food cultures of ancient civilizations which developed around the Mediterranean Basin and is based on the regular consumption of olive oil (as the main source of added fat), plant foods (cereals, fruits, vegetables, legumes, tree nuts, and seeds), the moderate consumption of fish, seafood, and dairy, and low-to-moderate alcohol (mostly red wine) intake, balanced by a comparatively limited use of red meat and other meat products. A few decades ago, the Mediterranean diet drew the attention of medical professionals by proving extended health benefits. The first reports a...

In this study, the synergistic/additive effects of combined supplementations with blueberry and yoghurt, and C3G and peptides were determined. Blueberry and yoghurt alone, and the combination of C3G and peptides significantly reduced both systolic and diastolic blood pressure in diet-induced obese mice. Yoghurt supplementation significantly reduced body weight, percentage body fat and improved intraperitoneal glucose tolerance. Furthermore, peptides and the combination of peptides and C3G resulted in a significant reduction of percentage body fat and improved intraperitoneal glucose tolerance. As widely available, safe and...

This study measured for the first time serum CCN3 levels in T2DM and explored the correlations between its serum levels and various metabolic parameters in humans.MethodsA total of 219 newly diagnosed T2DM (nT2DM) patients and 205 healthy control subjects, matched for age and sex ratio, were enrolled. Circulating CCN3 and TNF-α, IL-6 and MCP-1 were measured by ELISA. The anthropometric assessment and biochemical evaluation were done in all subjects. OGTT were performed in 34 healthy individuals to investigate the association of CCN3 with glucose.ResultsSerum CCN3 levels were significantly higher in nT2DM patients com...